Thursday, June 30, 2011

ME/CFS Exercise Study: Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome

This study by David Jones and others from Newcastle (never heard of them) is interesting, because just like Alan Light, these researchers found two subgroups in ME/CFS, when they challenge the patients with exercise.
Abstract
Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome
(via niceguidelines.blogspot.com)

Background:  Chronic fatigue syndrome (CFS) patients frequently describe difficulties with repeat exercise. Here we explore muscle bioenergetic function in response to 3 bouts of exercise.

Methods:  18 CFS (CDC 1994) patients and 12 sedentary controls underwent assessment of maximal voluntary contraction (MVC), repeat exercise with magnetic resonance spectroscopy and cardio-respiratory fitness test to determine anaerobic threshold.

Results:  CFS patients undertaking MVC fell into 2 distinct groups.

8 (45%) showed normal PCr depletion in response to exercise at 35% of MVC (PCr depletion >33%; lower 95% CI for controls).

10 CFS patients had low PCr depletion (generating abnormally low MVC values).

The CFS whole group exhibited significantly reduced anaerobic threshold, heart rate, VO2, VO2 peak and peak work compared to controls. Resting muscle pH was similar in controls and both CFS patient groups.

However, the CFS group achieving normal PCr depletion values showed increased intra-muscular acidosis compared to controls after similar work after each of the 3 exercise periods with no apparent reduction in acidosis with repeat exercise of the type reported in normal subjects.

This CFS group also exhibited significant prolongation (almost 4-fold) of the time taken for pH to recover to baseline.

Conclusion:  When exercising to comparable levels to normal controls CFS patients exhibit profound abnormality in bioenergetic function and response to it. Although exercise intervention is the logical treatment for patients showing acidosis any trial must exclude subjects who do not initiate exercise as they will not benefit. This potentially explains previous mixed results in CFS exercise trials.
So, to recap the little information the abstract gives: The CFS group exhibited significantly reduced anaerobic threshold, heart rate, VO2, VO2 peak and peak work compared to sedentary controls. Resting muscle pH was similar in controls and both CFS patient groups.

One half of the patients (remember, small study!) had low PCr depletion (Phosphocreatine?). (Are these the POTS patients?)

The other half of the patients showed normal PCr depletion (Phosphocreatine?) in response to exercise. However, this group showed increased intra-muscular acidosis compared to controls after similar work after each of the 3 exercise periods with no apparent reduction in acidosis with repeat exercise of the type reported in normal subjects. This group also exhibited 4-fold prolongation of the time taken for pH to recover to baseline.

I wonder how these groups map unto the two groups Alan Light found. Again, the "no apparent reduction with repeat exercise" is basically the same thing that other researcher see, that ME/CFS is something substantially different than deconditioning.
We observed that CFS patients as a group have reduced cardio-respiratory reserve with a lower anaerobic threshold than sedentary controls. This finding replicates previous studies [3]. One implication of a lowered anaerobic threshold would be increased reliance on anaerobic as opposed to aerobic metabolism with a predicted consequence of increased short term acid generation within muscle due to over-utilization of the lactate dehydrogenase pathway. This prediction was confirmed by the use of MR spectroscopy methodologies which demonstrated increased post-exercise acidosis in the CFS group as a whole. The effect was not, however, uniform across the CFS patient group. 
In the CFS subjects where normal PCr depletion was seen in the context of a normal MVC, exercise induced profound and sustained acidosis. This replicates our previous findings [18] in a second cohort of patients with CFS. Importantly, minimum pH values attained by this group of CFS patents were actually lower than those previously shown by us in the fatigue-associated chronic disease primary biliary cirrhosis (PBC) [28]. We would suggest that the increased reliance upon anaerobic metabolism during even relatively lowlevel muscle contraction, shown by a decreased intramuscular pH, is at least partly a consequence of the decreased aerobic capacity (reduced anaerobic threshold and VO2peak) seen in CFS, and in this regard the physiology of fatigue in CFS closely mirrors that in PBC.

There are aspects of the abnormality in acid homeostasis in CFS which differ to those seen in PBC and which may significantly contribute to the severity of fatigue in CFS. We have previously reported that when PBC patients undergo repeat exercise the degree of acidosis seen within muscle reduces with each exercise episode, suggesting the retention of some compensatory capacity for excess muscle acidosis in PBC (28). One mechanism for this is increase in proton flux, and the speed of onset of maximum proton excretion, with repeat exercise. This phenomenon, which is also a feature of mitochondrial disease where increased proton efflux after exercise helps compensate for reduced aerobic capacity [35], was absent from the CFS patients. These findings suggest that CFS patients are unable to compensate for the increased reliance upon anaerobic energy sources during muscle contraction in comparison to other conditions with reduced aerobic capacity. The net effect of these combined effects can be seen in terms of cumulative acid exposure determined from the area under the curve for pH. Using this approach total post-exercise acid exposure is of the order of 50-fold higher in CFS patients exercising to the same degree as normal controls, with no reduction in this pattern of sustained high level acidosis with repeat exercise. We believe that the local and systemic sequelae of this sustained acid exposure contribute significantly to the expression of fatigue in CFS.

The reasons for slowed recovery from muscle acidosis in CFS are at present unclear but there are a number of possibilities. Our finding of a slow recovery time appears to be at least in part a result of slow kinetics of proton excretion and may point to potential mechanisms by which the increased muscle acid exposure occurs. Acid is actively transported from the muscle by Na-H antiporters which are in turn under autonomic regulation. Indeed, conditions which increase sympathetic tone such, as hypertension [36], or following sympathetic denervation [37] change acid handling in muscle. It is possible that impaired function of acid transporters occurs in CFS and that this related to the autonomic dysfunction found frequently in those with CFS [2, 19-22]. It is also possible that reduced vascular run off (related to autonomic dysregulation) may also contribute. Furtherwork is needed to explore the underlying mechanisms fully. Importantly, many of the pathways for acid excretion from muscle cells can be upregulated by exercise therapy suggesting a possible mechanism for benefit with graded exercise therapy (although our caveats about stratification should be noted).  
"I think the Lights should take this finding on board when they find increased acid sensors - that it's most likely because there's increased acid!" 

3 comments:

  1. As in many of these ridiculous papers, they find actual physical pathology and then in the conclusion warp it some way to suggest GET and/or psychogenesis.

    The last two sentences are very troubling to me. It says that ME should be treated with 'exercise intervention' (GET) because this is the proper treatment for acidosis. Also says that pw"CFS" who do not normally exercise should be excluded from any study because they may not comply with the GET instructions and thus artificially lower the measured effectiveness of GET in trials like PACE. Obviously, if pw-Oxford defined "CFS" who normally exercise are studied, all of the people in the study will have Idiopathic Chronic Fatigue not ME.

    ReplyDelete
  2. The "no apparent reduction in acidosis with repeat exercise" says quite clearly: You can't push through the pain in ME/CFS.

    It is an shame if the research misinterpret their own data in such a way that they state that exercise intervention could be a viable form of treatment for ME/CFS. But that is unfortunately the state of science in general, not only in ME/CFS: Researchers find something that doesn't fit their believes and they either call it a "paradox" or they blame the test subjects... See this: "Subjects on low-fat diets systematically underreport energy intake compared with subjects on low carbohydrate diets."

    ReplyDelete
  3. And one more important thing is the comparison between patients with ME/CFS and sedentary controls shows quite clearly that the problem isn't lack of exercise, that the pathologic problem is something quite different.

    To restate: You can't exercise ME/CFS away, like you would treat deconditioning. (But that doesn't mean you should do no exercise: with carefully staying within the limits, like you would do with a heart-disease, you can slightly improve your condition in ME/CFS, which is something one should not despise.)

    ReplyDelete

Comments are most welcome! But please:

- No SPAM whatsoever, no supplements, no pharmaceuticals, no herbs or any other advertisements

- Absolutely no quack-doctors pushing their quack-BS websites (and if you are a quack, I will call you out)

- Be critical if you want to, but try to be coherent

Comments are moderated, because I am tired of Gerwyn-V99-The-Idiot and his moronic sockpuppets, and tired of the story of the two dogs, but I will try to publish everything else.

If you are not Gerwyn (and want to tell me something other than the story of the two dogs), then relax and write something! :-)

Labels

5-AZA A. Melvin Ramsay Acne Advocacy Alan Light Alternative medicine is an untested danger Ampligen Andrew Wakefield Anecdote Anthony Komaroff Antibiotics Antibodies Anxiety Aphthous Ulcers Apnea Asthma Autism Autoimmune Disease Behçet’s Ben Katz Bertrand Russell Biology Blood sugar Bruce Carruthers Caffeine Calcium Cancer Capitalism Cardiology Carmen Scheibenbogen CBT/GET CDC Celiac Disease Cereal Grains CFIDS Chagas Charité Charles Lapp Christopher Snell Chronix Clinician Coconut Milk Cognition Common Sense and Confirmation Bias Conversion Disorder Coxiella Burnetii Coxsackie Criteria Crohn's Cushing's Syndrome Cytokine Daniel Peterson Darwinism David Bell Depression Diabetes Diagnostic Differential Disease Diseases of Affluence DNA DNA Sequencing Dog DSM5 EBV EEG Eggs Elaine DeFreitas Elimination Diet Enterovirus Epstein-Barr ERV Etiology Evolution Exercise Challenge Faecal Transplant Fame and Fraud and Medical Science Fatigue Fatty Acids Fibromyalgia Francis Ruscetti Fructose Gene Expression Genetics Giardia Gordon Broderick Gulf War Illness Gut Microbiome Harvey Alter Health Care System Hemispherx Hemolytic Uremic Syndrome Herpesviridae High Blood Pressure Historic Outbreaks HIV HPV Hyperlipid Ian Hickie Ian Lipkin Immune System Infection Intermittent Fasting It's the environment stupid Jacob Teitelbaum Jamie Deckoff-Jones Jo Nijs John Chia John Coffin John Maddox José Montoya Judy Mikovits Karl Popper Kathleen Light Kenny De Meirleir Lactose Lamb Laszlo Mechtler LCMV Lecture Leonard Jason Leukemia Life Liver Loren Cordain Low Carb Low-Dose Naltrexone (LDN) Luc Montagnier Lucinda Bateman Ludicrous Notions Lumpers and Splitters Lyme Mady Hornig Mark Hasslett Martin Lerner Mary Schweitzer MCS ME/CFS Medical Industry Medicine is not based on anecdotes Michael Maes Migraine Milk and Dairy Mitochondria MMR Money and Fame and Fraud MRI Multiple Chemical Sensitivity Multiple Sclerosis Mutton My Symptoms n-1 Nancy Klimas Narcolepsy Neurodermitis Neuroscience NK-Cell Nocebo NSAID Nutrition Obesity On Nutrition Pain Paleo Parathyroid Pathogen Paul Cheney PCR Pharmaceutical Industry Picornavirus Placebo Polio Post Exertional Malaise POTS/OI/NMH PTSD PUFA Q Fever Quote Rare Disease Research Retrovirus Rheumatoid Arthritis Rituximab RNA Robert Gallo Robert Lustig Robert Silverman Robert Suhadolnik Rosario Trifiletti Sarah Myhill Sarcasm Science Sequencing Seth Roberts Shrinks vs. Medicine Shyh-Ching Lo Simon Wessely Sinusitis Sjögren's Somnolence Sonya Marshall-Gradisnik Speculation Stanislaw Burzynski Statins Stefan Duschek Study Sucrose Sugar Supplements Symptoms T1DM T2DM There is no such thing as Chronic Lyme There is no such thing as HGRV Thyroid Tinitus To Do Toni Bernhard Tourette's Treatment Tuberculosis Vaccine Video Vincent Lombardi Vincent Racaniello Virus Vitamin B Vitamin D VP62 When Evidence Based Medicine Isn't Whooping Cough Wolfgang Lutz WPI XMRV You fail science forever